It is the long-range purpose of this project to study how various chemicals and physiological changes affect xenobiotic metabolism by the body. This laboratory has concentrated its effort on the lung as a target organ for exposure to environmental stresses. Present studies include isolation of rabbit lung cell types for the purpose of studying localization of xenobiotic metabolism within the lung and toxication-detoxication mechanisms in individual cell populations. The following model enzyme systems are being used for study of individual xenobiotic metabolic pathways in lung cell populations: coumarin hydroxylase, 7-ethoxycoumarin deethylase, benzo(a)pyrene hydroxylase, and N,N-dimethylaniline N-oxidase. Different lung cell fractions (mixed cell populations) appear to have different metabolic profiles indicating possible differences in cytochrome content in the cell types. Cell fractions containing alveolar type II cells and nonciliated bronchiolar epithelial cells (Clara cells) are being further purified for detailed studies of mixed-function oxidase activity.